Biomedical subjects

T M Wheeler

Publications and source records attributed to T M Wheeler.

At least 91 records · Page 5Linked to original sources

PubMed1995

The frequency of apoptosis correlates with the prognosis of Gleason Grade 3 adenocarcinoma of the prostate.

BACKGROUND: Although localized carcinomas are predominantly moderately differentiated (Gleason Grade 3), they demonstrate markedly different rates of progression. Previously, the authors reported a correlation between apoptosis and the malignant characteristics of carcinoma in the mouse prostate reconstitution model system and between apoptosis and Gleason grade in the human tumor. This study was undertaken to determine whether the frequency of apoptosis correlates with prognosis and to compare the prognostic significance of the apoptotic index with other prognostic features in Gleason Grade 3 carcinomas. METHODS: The apoptotic and mitotic indices of malignant and nonmalignant epithelium in 28 consecutive radical prostatectomy specimens were determined for a carcinomas composed entirely of Gleason sum 6 (primary Grade 3, secondary Grade 3) with a clinical stage T2 classification. Each patient was followed for 5-9 years (median 6, years). The indices, defined as the number of apoptotic and mitotic bodies in an H & E-stained section per 100 grids delineated by an ocular measuring field, were determined. The actuarial time to progression, defined as a sustained rise in the serum prostate specific antigen level greater than or equal to 0.4 ng/ml, was correlated with the apoptotic index, the mitotic index, tumor volume, and pathologic stage. RESULTS: Neither pathologic stage nor tumor volume differed significantly between the group of 19 patients (68%) with no progression and the other 9 whose tumor progressed. The median apoptotic index of the carcinomas was 0.87 (range, 0.12-3.91). For patients with a low apoptotic index (< 0.87), the actuarial progression rate at 5 years was 7% +/- 14% (+/- 2 SE) compared with 50% +/- 26% for those with a high apoptotic index (P < 0.007). Mitotic index had no prognostic significance. CONCLUSIONS: In carcinoma of the prostate, apoptosis can be recognized in standard H & E sections and quantitated by light microscopy. The apoptotic index may provide additional prognostic information in the predominant grade of early stage carcinoma. Cancer 1995; 75:522-9.

Adenocarcinoma↗

PubMed1995

Leu-7 immunoreactivity in cytologic specimens of thyroid lesions, with emphasis on follicular neoplasms.

Anti-Leu-7 (HNK-1, CD 57) antibody, a marker for natural killer lymphocytes, was employed by Ghali et al. (Hum Pathol 1992;23: 21-25) to study surgically resected formalin-fixed, paraffin-embedded thyroid lesions. They demonstrated strong immunoreactivity of this antibody with thyroid carcinomas, both follicular and papillary, and only occasional weak immunoreactivity with colloid goiters and follicular adenomas. We studied cytologic specimens (primarily fine-needle aspiration biopsy specimens) from 44 thyroid lesions, including 10 follicular carcinomas, 14 follicular adenomas, seven adenomatous nodules, six papillary carcinomas, and seven cases of Hashimoto's thyroiditis. All follicular carcinomas exhibited immunoreactivity to anti-Leu-7 antibody, usually of a moderate to strong degree (9/10); however, six of 14 follicular adenomas yielded similar results. The patterns of immunoreactivity in the other lesions were similar to those previously described (Ghali et al., Hum Pathol 1992;23:21-25). It does not appear that anti-Leu-7 antibody can be used as a specific marker of malignancy in the cytologic assessment of follicular neoplasms of the thyroid.

Adenocarcinoma, Follicular↗

PubMed1995

Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the epididymis.

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel-Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.

Adenocarcinoma, Clear Cell↗

PubMed1995

High grade prostatic intraepithelial neoplasia in prostates removed following irradiation failure in the treatment of prostatic adenocarcinoma.

Prostatic Intraepithelial Neoplasia (PIN) is widely considered to be a precursor lesion for adenocarcinoma of the prostate. No information is available, however, on the sensitivity of PIN to irradiation or the distribution of residual PIN after radiotherapy. We studied a series of forty-six totally embedded, whole mounted, serially sectioned prostates removed by salvage radical retropubic prostatectomy following irradiation failure in which no hormonal therapy/ablation had been undertaken. The mean age of patients was 65 (56-74) years, the mean dose of radiotherapy was 7,266 (6,000-9,000) cGy (15 external beam, 27 external beam plus iridium or gold seed, 3 iodine, and 1 unknown) and the mean interval for irradiation therapy to prostatectomy was 60 (16-145) months. Thirty-two (70%) of the patients had high grade PIN within the prostatectomy specimen. The pattern of PIN was recorded as described by Bostwick and co workers. The frequency of the different patterns per positive case paralleled in rank those in Bostwick's series of non-irradiated prostates, with the most common to least common per patient being: tufting (78.1%), micropapillary (59.3%), cribriform (34.4%) and flat (15.6%). However, the mean number of foci of PIN per prostate was less than in Bostwick's series (7.1 foci vs. 17 foci). There was no statistically significant difference between groups with or without high grade PIN with regard to various clinical factors (last preoperative serum PSA, age, dose of radiotherapy, interval from irradiation therapy to prostatectomy, Kaplan-Meier survival), or pathologic factors (presence of confined tumor, extracapsular extension, positive surgical margins, seminal vesicle invasion, or positive lymph nodes on permanent sections). We conclude that high grade PIN is common in the prostates of patients who have failed irradiation therapy and that, theoretically, not all recurrent tumors derive from regrowth of the initial, incompletely eradicated tumor. However, because there was no significant difference between the two groups with regard to the clinical and pathologic parameters listed, we consider it likely that most recurrent tumors derive from the initial incompletely eradicated tumor.

Adenocarcinoma↗

PubMed1995

Verumontanum mucosal gland hyperplasia in prostatic needle biopsy specimens. A mimic of low grade prostatic adenocarcinoma.

The histologic features of five cases of verumontanum mucosal gland hyperplasia (VMGH) in prostatic needle biopsy specimens are reported. All cases were initially reviewed in consultation by one of two of the authors (JIE or TMW) and in all cases, the submitted differential diagnosis included low grade adenocarcinoma. In all cases, VMGH was characterized by a relatively well-circumscribed collection of closely packed glands, and was typically observed immediately subjacent to urothelium. A basal cell layer was readily identifiable in routine hematoxylin-and-eosin-stained sections. The luminal contents of the verumontanum mucosal glands were distinctive and consisted of lamellated eosinophilic concretions typical of corpora amylacea, as well as unique orange-red concretions that were commonly fragmented. The histologic features of VMGH are characteristic and allow distinction from other small glandular proliferations of the prostate including nephrogenic adenoma, adenosis (atypical adenomatous hyperplasia), and low grade adenocarcinoma.

Adenocarcinoma↗

PubMed1995

Verumontanum mucosal gland hyperplasia.

Prostatic adenocarcinoma of the small acinar type can be mimicked by benign proliferative lesions, such as atypical adenomatous hyperplasia (adenosis), sclerosing adenosis, nodular hyperplasia (cellular areas), lobular hyperplasia, basal cell hyperplasia, mesonephric hyperplasia, and nephrogenic adenoma. In our study, we describe another microacinar proliferation, which we have termed verumontanum mucosal gland hyperplasia (VMGH) because it occurs exclusively in the verumontanum and adjacent posterior urethra where the ejaculatory ducts and utricle empty into the urethra. We reviewed 341 radical prostatectomies and cystoprostatectomies done from 1988 through 1993 for prostate and bladder carcinoma, respectively. Forty-nine prostates (14%) from patients aged 47 to 87 contained foci of VMGH. Of a total of 88 foci, a single lesion was present in 19 cases and multiple lesion in 30 cases. Fifty-nine of the foci arose around the ejaculatory or prostatic ducts, 17 from around the utricle, and 13 from adjacent posterior urethral mucosa. Individual lesions were quantified as to the number of acini per focus as follows: 6 to 10 in 28 (1+), 11 to 25 in 29 (2+), 25 to 50 in 16 (3+), and more than 50 in 15 (4+). No crystalloids or intraluminal mucin were seen, but; intraluminal corpora amylacea, usually numerous, were present in 57 of the 88 voci. The microacini were frequently "back to back" architecturally. The lining epithelium consisted of bland cuboidal to columnar luminal cells with underlying basal cells. VMGH, a previously undescribed benign microacinar proliferation, occurs in a very restricted and specific location and appears to be unrelated to other lesions with which it may be confused.

Aged↗

PubMed1995

Interobserver reproducibility in the diagnosis of prostatic intraepithelial neoplasia.

To assess interobserver reproducibility in the categorization of prostatic intraepithelial neoplasia (PIN) seven pathologists reviewed 25 lesions. Rather than classic or consecutive examples of PIN, cases were selected to represent the full spectrum of diagnostic issues in this field. Lesions were classified into one of six categories: (a) benign prostate tissue, (b) PIN1, (c) PIN2, (d) PIN3, (e) PIN3 cannot rule out associated cancer, and (f) PIN3 plus cancer. Following evaluation of the slides, data were also analyzed by combining several of the groups into three categories: (a) benign/PIN1; (b) PIN2/PIN3/PIN cannot rule out cancer; and (c) PIN plus cancer. The level of agreement was fair (Kappa = 0.33) for the six categories and substantial (Kappa = 0.61) for the three groups. In no case was there a uniform diagnosis of PIN1; in all cases at least some pathologists considered the biopsies to be normal. This finding provides support for not commenting on PIN1 in biopsy material. In general, there was good distinction between low-grade PIN (PIN1) and high-grade PIN (PIN2-3). Among the seven cases for which there was a consensus that the lesion represented high-grade PIN, there was no case in which there was uniform agreement as to whether the lesion represented PIN2 or PIN3. This finding supports combining PIN2 and PIN3 into high-grade PIN. Cases classified as low-grade PIN by some and as high-grade PIN by others were those with pleomorphism but without prominent nucleoli. Difficulties in distinguishing "high-grade PIN" from "high grade PIN cannot rule out cancer" were those with cribriform glands, glands with necrosis, and where high-grade PIN was associated with only a few adjacent small atypical glands. These same histologies caused the participating pathologists difficulty in distinguishing "high-grade PIN cannot rule cancer" from "high grade PIN plus cancer."

Biopsy, Needle↗

PubMed1995

Salvage radical prostatectomy: outcome measured by serum prostate specific antigen levels.

We reviewed our experience with salvage radical prostatectomy for locally recurrent cancer in 40 patients to assess the current complication rate and the results using prostate specific antigen (PSA) as an indicator of treatment outcome and to identify better criteria for the selection of appropriate candidates for this operation. Most recurrent cancers were detected by digital rectal examination (26 patients) or increasing serum PSA levels (10). The operation was technically challenging, with 6 rectal injuries (15%), 2 requiring temporary colostomy. Serious technical complications were more common (31%) among the 29 patients who underwent pelvic lymphadenectomy at the time of initial radiotherapy than among the 11 treated with external irradiation alone (9%). Urinary incontinence persisted in 18 of 31 evaluable patients (58%) and was successfully corrected with an artificial urinary sphincter in 9. A total of 21 patients (54%) had pathologically advanced disease (seminal vesicle invasion and/or lymph node metastases). Preoperative PSA levels but not clinical stage or biopsy grade correlated with pathological stage (p < 0.03). If the PSA was less than 10 ng./ml. only 15% of the patients had an advanced pathological stage, compared to 86% if the PSA was 10 or more. After 2 to 97 months (mean 39) 2 patients died of metastatic prostatic cancer, 5 had distant metastases and none had symptomatic local recurrence. At 5 years the actuarial nonprogression rate measured by PSA was 55 +/- 20%. The only pretreatment factor predictive of progression was the serum PSA level. If the PSA was less than 10 ng./ml. the actuarial rate of progression was significantly lower than if the PSA was greater than 10 (p < 0.05). The best results were in the subset of 18 patients with cancer confined to the prostate or immediate periprostatic tissue: 82% had no progression at 5 years. Within each of these pathological stages the results of salvage prostatectomy were similar to those for standard radical prostatectomy in patients with no prior irradiation. Although technically challenging, salvage prostatectomy provides excellent control of radio-recurrent cancer confined to the prostate or immediate periprostatic tissue and is best performed before the preoperative PSA level increases to greater than 10 to 20 ng./ml.

Aged↗

PubMed1995

Pelvic lymph node histiocytosis mimicking metastatic prostatic adenocarcinoma: association with hip prostheses.

PURPOSE: Histological changes in lymph nodes simulating metastatic prostatic adenocarcinoma are reported. MATERIALS AND METHODS: Lymph node frozen sections from 3 patients with prostatic cancer displayed marked histiocytosis. This tissue was subjected to histochemical, immunohistochemical and electron microscopic studies. RESULTS: Only 1 erroneous diagnosis of metastasis was made. All patients had hip prostheses for at least 6 years. Tissue replacing up to 80% of lymph nodes consisted of histiocytes containing large amounts of polyethylene. CONCLUSIONS: Hip replacement predisposes the patient to have pelvic lymph node histiocytosis mimicking metastatic adenocarcinoma. This history should be communicated to the pathologist. Polyethylene is the most important factor in the cause of post-prosthesis lymph node histiocytosis.

Adenocarcinoma↗

PubMed1995

Prognostic significance of positive surgical margins in radical prostatectomy specimens.

PURPOSE: The prognostic significance of positive surgical margins in radical prostatectomy specimens was assessed. MATERIALS AND METHODS: The interval to progression (increasing prostate specific antigen level) was measured in 478 patients by status of the surgical margins. RESULTS: At 5 years, the nonprogression rate was 64% for patients with and 83% for those without positive surgical margins. With a high grade cancer, seminal vesicle invasion or lymph node metastases, positive surgical margins had no effect on prognosis; with extracapsular extension and a Gleason score of 6 or less positive surgical margins were associated with a higher progression rate. CONCLUSIONS: Prognosis was adversely affected by positive surgical margins only in moderately differentiated cancers with extracapsular extension alone. If the cancer is otherwise confined, positive surgical margins are associated with an excellent prognosis unlikely to be improved by adjuvant therapy.

Actuarial Analysis↗

PubMed1995

Association of p53 mutations with metastatic prostate cancer.

In prostate cancer, mutation of the p53 tumor suppressor gene has been associated with locally advanced disease and hormone-resistant disease that is predominantly localized to bone. However, little is known regarding the status of the p53 gene in metastatic prostate cancer that has not been treated with hormonal manipulation. We evaluated formalin-fixed, paraffin-embedded malignant tissues from 86 patients with various stages of prostate cancer, including pathologically confined, locally advanced, and metastatic disease, to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. No abnormal p53 immunostaining was detected in 18 patients with prostate cancer confined to the gland. Two tumors from 21 patients with locally advanced disease (extracapsular extension and/or seminal vesicle invasion) had abnormal nuclear p53 accumulation, and a mutation in exon 7 of the p53 gene was detected in tumor DNA from one patient using single-strand conformation polymorphism-direct sequencing analysis. Of the remaining 47 patients studied in whom tissues from the prostate gland and a metastatic site (44 lymph node, 2 bone, and 1 lung) were available, only 3 had received hormonal therapy prior to obtaining metastatic tissue. In four patients both primary and metastatic tumors demonstrated accumulation of p53 protein, whereas seven additional patients exhibited p53 accumulation only at the metastatic site. In three patients the metastatic tumors harbored missense single-base substitutions in exon 5, as detected using single-strand conformation polymorphism-direct sequencing. These results indicate that p53 abnormalities are associated with lymph node metastases derived from prostate cancer patients that had not undergone hormonal therapy.

Adenocarcinoma↗

PubMed1994

The New American Joint Committee on Cancer and International Union Against Cancer TNM classification of prostate cancer. Clinicopathologic correlations.

BACKGROUND: The 1992 American Joint Committee on Cancer and International Union Against Cancer TNM classification system for prostate cancer includes categories for the increasingly common nonpalpable cancers detected by serum prostate specific antigen (PSA) levels and transrectal ultrasonography (TRUS), but few details have been published about the pathologic features and prognosis of such cancers. METHODS: We analyzed the clinical and pathologic features of 400 patients with clinical Stages T1-T3, NO or NX, M0 cancer treated with radical prostatectomy. We compared volume, grade, extension, and prognosis of cancers detected by PSA or TRUS to those detected by the traditional techniques of transurethral resection (TURP) or digital rectal examination. RESULTS: As clinical stage increased in the TNM classification, the volume, grade, and frequency of extraprostatic spread increased significantly. The 33 nonpalpable, nonvisible tumors detected because of an elevated PSA (T1c) were similar in size and frequency of extension to TURP-detected (T1a-b) cancers, but more often were poorly differentiated (52% vs. 22%) (P < 0.03). No T1c cancer has recurred to date. Nonpalpable T2 cancers detected by TRUS (n = 42) were significantly more likely (47% vs. 18%) to extend outside the prostate than were T1c cancers. Compared to palpable T2 cancers, TRUS-detected T2 cancers were smaller but were similar in grade, extension, and prognosis. T3 cancers were extensive and recurred rapidly; only 6% were confined to the prostate. In contrast, 24% of the T1 and 57% of the T2 cancers were not confined (> or = pT3), but only 6-9% of T1-T2a cancers exhibited advanced pathologic features (seminal vesicle invasion or lymph node metastases), compared with 26% of the T2b-c cancers. CONCLUSION: The new TNM staging system provides appropriate new categories for inclusion of nonpalpable cancers detected by PSA and ultrasound. This new classification is logical and generally reflects the pathologic extent and prognosis of these tumors, although cancers in the advanced T2 categories are often more extensive.

Adult↗

PubMed1994

DNA ploidy measurements in prostate cancer: differences between image analysis and flow cytometry and clinical implications.

The relationship between DNA ploidy and prognostic parameters has been established in prostate cancer. However, comparison of various techniques used for DNA ploidy analysis has not been sufficiently addressed in prostate carcinoma. In the present study, grossly identified discrete carcinoma foci from 48 consecutive radical prostatectomy specimens were analyzed by flow cytometry and image analysis using both imprints and tissue sections. Correlations with other prognostically important pathological findings such as grade, size, extracapsular extension, positive surgical margin, and seminal vesicle and lymph node involvement were done. Image analysis detected 26 (54.2%) nondiploid tumors compared to 15 (31.3%) nondiploid tumors by flow cytometry. No significant differences were demonstrated between imprints and tissue sections. DNA ploidy status showed a good correlation with most other pathological findings listed above. In conclusion, DNA ploidy status determination gives clinically useful information which correlates well with the other useful pathological parameters of prognostic importance. Image analysis may be more sensitive than flow cytometry in detecting nondiploid populations. Tissue sections appear to be as reliable as imprints when properly controlled.

Adenocarcinoma↗

PubMed1994

Fresh tissue harvest for research from prostatectomy specimens.

As a consequence of molecular biological and genetic techniques, the demand for fresh tissue for basic research has increased dramatically at academic medical centers. Because of the extreme lability of many biological macromolecules, tissue must be harvested with the least possible delay from the time of removal. This necessity for quick action, frequently under less than optimal circumstances, along with the obvious loss of tissue available for diagnostic purposes, presents a daunting challenge to the pathologist responsible for accurate grading and staging of the cancer. A novel approach is described for the procurement of fresh and freshly frozen prostatic tissue with acceptable limitations on subsequent morphological analysis.

Adult↗

PubMed1994

Frequency of apoptotic bodies positively correlates with Gleason grade in prostate cancer.

Tissue samples from patients with carcinoma of the prostate of various Gleason grades were examined for the frequency of apoptotic bodies. Apoptotic bodies were scored by morphometric methods using hematoxylin-eosin (HE)-stained sections from surgical specimens of prostate cancer. Non-neoplastic prostate tissue adjacent to foci of cancer showed a very low frequency of apoptotic bodies. Significantly larger numbers of apoptotic bodies were observed in the areas of carcinoma than in the non-neoplastic control tissues, regardless of Gleason grade. Interestingly, a positive correlation was noted between apoptotic bodies and increasing Gleason grade. The positive correlation suggests that increased programmed cell death is a feature of the increasing malignant potential that is associated with higher Gleason grade in prostate cancer.

Adult↗

PubMed1994

The pathological features and prognosis of prostate cancer detectable with current diagnostic tests.

The discrepancy between the high prevalence of prostate cancer found at autopsy and the low incidence of clinical cancer prompted a study to determine whether the new diagnostic tests, that is ultrasonography and serum prostatic specific antigen (PSA) levels, detect prostate cancer at an earlier stage than the traditional test, digital rectal examination, without detecting a larger proportion of clinically unimportant cancer. Clinically detected cancer treated by radical prostatectomy (306 cases) and incidental cancer found in cystoprostatectomy specimens (90) were categorized into 3 groups by the volume, grade, extent of the cancer and outcome of treatment: clinically unimportant tumor (0.5 cm.3 or less, Gleason grades 1 to 3 and confined to the prostate), clinically important curable cancer (more than 0.5 cm.3 or grade 4 or 5 and confined, or with microscopic extracapsular extension) or advanced disease (extensive extracapsular extension, seminal vesicle invasion or lymph node metastases). Of 306 clinically detected tumors 9% were unimportant and 29% were advanced. In contrast, incidental cystoprostatectomy disease was either unimportant (78%) or curable (22%) and no tumor was advanced (p < 0.0005). Cancer detectable by digital rectal examination, ultrasonography or PSA was distributed similarly among the 3 groups. Impalpable cancer detected by PSA was less likely to be advanced (11%) than cancer detected by digital rectal examination (34%, p = 0.01) but no more likely to be unimportant (13% versus 8%). Of 29 tumors detected only by systematic biopsies because of an elevated PSA level only 4% were advanced, while 17% were unimportant. Cancer detectable with each of the available diagnostic tests was similar and differed distinctly from that found incidentally in cystoprostatectomy specimens. The detection of impalpable cancer by PSA or ultrasound decreased the proportion of advanced tumor detected without increasing significantly the detection of unimportant disease.

Adult↗

PubMed1994

Can radical prostatectomy alter the progression of poorly differentiated prostate cancer?

A favorable outcome after radical prostatectomy for early stage prostate cancer has sometimes been attributed to the relatively benign natural history of the disease rather than the beneficial effects of treatment. Poorly differentiated tumors, however, are recognized as inherently aggressive and progress rapidly when managed conservatively. We determined the actuarial rate of treatment failure after radical prostatectomy for clinically localized (stages T1 to T3) poorly differentiated cancer, using as an end point an increase in the serum level of prostate specific antigen (PSA) to assess whether treatment altered the rapid progression expected of these cancers. Of 500 patients treated with radical prostatectomy, regardless of grade, the actuarial nonprogression rate was 76 +/- 5% at 5 years and 73 +/- 6% at 10 years. Poorly differentiated cancer, defined as Gleason score 7 or greater in the radical prostatectomy specimen, was present in 268 patients (54%) who had a nonprogression rate at 5 years of 55 +/- 12% compared to 92 +/- 4% for the 232 patients with a well or moderately differentiated (Gleason score less than 7) cancer (p < 0.00005). The extent of the cancer (confined or not confined) was strongly associated with progression (p < 0.00005). Only 76 of the 268 poorly differentiated tumors (28%) were confined to the prostate and the prognosis was excellent. At 5 years 85 +/- 18% of the patients had no evidence of progression, compared to 46 +/- 12% with poorly differentiated cancer extending outside the gland (p < 0.0001). In a multivariate analysis neither the grade nor volume of the tumor influenced the rate of progression when the cancer was confined to the prostate. Impalpable tumors detected by an elevated PSA level were as likely to be poorly differentiated as palpable disease (56% versus 63%) but were significantly more likely to be confined to the prostate (44% versus 24%, p < 0.01). Poorly differentiated cancers usually extend outside of the prostate by the time they are detected, and they progress rapidly. PSA increases the detection of impalpable high grade cancer confined to the gland. When these tumors are detected while still confined, most can be controlled by radical prostatectomy.

Actuarial Analysis↗

PubMed1994

Some small prostate cancers are nondiploid by nuclear image analysis: correlation of deoxyribonucleic acid ploidy status and pathological features.

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p < 0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.

Cell Nucleus↗